COMPARISON OF CYTOSOLIC CALCIUM SHIFTS, SUPEROXIDE GENERATION, AND LACTOFERRIN SECRETION IN THE NEUTROPHILS OF ATOPICS AND NONATOPICS

We previously found that platelet-activating factor (PAF) stimulated g reater lactoferrin secretion by neutrophils of atopics than nonatopics . To help understand underlying mechanisms, we compared agonist-stimul ated lactoferrin secretion with another response, superoxide generatio n, to determine whether there is a global alteration in the reactivity of atopic neutrophils to these stimuli. We also determined Ca2+ mobil ization in such neutrophils because such mobilization is a signaling p athway for both superoxide generation and granule content exocytosis. Although PAF again stimulated greater lactoferrin secretion in atopic than in nonatopic neutrophils, the peak superoxide secretion and cytos olic Ca2+ mobilization were not significantly different in atopics and nonatopics. Leukotriene B4-induced superoxide secretion and cytosolic Ca2+ shifts were also similar in atopics and nonatopics. These findin gs suggest that (1) the enhanced PAF-induced lactoferrin secretion in atopic neutrophils is not a reflection of greater PAF binding or broad -based cell hyperreactivity and (2) a selective signaling pathway in a topic neutrophils may be responsible for the enhanced lactoferrin secr etion. These findings may be relevant to in vivo events because we hav e found increased PAF and lactoferrin release in skin chambers overlyi ng immunoglobulin E-mediated human skin reactions.